ES2572908T3 - Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa - Google Patents

Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa Download PDF

Info

Publication number: ES2572908T3
Authority: ES; Spain
Prior art keywords: alkyl; group; alkylene; substituted; phenyl
Prior art date: 2011-10-14
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Active

Application number

ES12778912.1T

Other languages

English (en)

Spanish (es)

Inventor

Michael J. Orwat

Donald J.P. Pinto

Leon M. Smith Ii

Shefali SRIVASTAVA

James R. Corte

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2011-10-14

Filing date

2012-10-12

Publication date

2016-06-03

2012-10-12 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

2016-06-03 Application granted granted Critical

2016-06-03 Publication of ES2572908T3 publication Critical patent/ES2572908T3/es

Status Active legal-status Critical Current

2032-10-12 Anticipated expiration legal-status Critical

Links

239000003112 inhibitor Substances 0.000 title description 55
108010080805 Factor XIa Proteins 0.000 title description 36
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 title description 7
125000000217 alkyl group Chemical group 0.000 claims abstract description 322
-1 -OH Chemical group 0.000 claims abstract description 177
150000001875 compounds Chemical class 0.000 claims abstract description 177
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 70
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 64
150000003839 salts Chemical class 0.000 claims abstract description 63
125000005843 halogen group Chemical group 0.000 claims abstract description 61
229910052760 oxygen Inorganic materials 0.000 claims abstract description 51
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 50
229910052717 sulfur Inorganic materials 0.000 claims abstract description 50
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 48
125000005842 heteroatom Chemical group 0.000 claims abstract description 42
125000002947 alkylene group Chemical group 0.000 claims abstract description 32
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 29
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 18
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 13
229910003813 NRa Inorganic materials 0.000 claims abstract description 9
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 3
229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 376
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 57
208000035475 disorder Diseases 0.000 claims description 55
208000007536 Thrombosis Diseases 0.000 claims description 52
230000009424 thromboembolic effect Effects 0.000 claims description 52
238000000034 method Methods 0.000 claims description 49
125000003545 alkoxy group Chemical group 0.000 claims description 34
229910052731 fluorine Inorganic materials 0.000 claims description 32
238000011282 treatment Methods 0.000 claims description 32
239000012453 solvate Substances 0.000 claims description 30
206010047249 Venous thrombosis Diseases 0.000 claims description 21
239000008194 pharmaceutical composition Substances 0.000 claims description 21
229910052799 carbon Inorganic materials 0.000 claims description 19
210000004369 blood Anatomy 0.000 claims description 17
239000008280 blood Substances 0.000 claims description 17
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
125000000753 cycloalkyl group Chemical group 0.000 claims description 14
208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 13
208000006011 Stroke Diseases 0.000 claims description 13
229910052801 chlorine Inorganic materials 0.000 claims description 13
238000002560 therapeutic procedure Methods 0.000 claims description 13
201000001320 Atherosclerosis Diseases 0.000 claims description 12
125000004429 atom Chemical group 0.000 claims description 12
125000001188 haloalkyl group Chemical group 0.000 claims description 11
208000010125 myocardial infarction Diseases 0.000 claims description 11
125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
206010003178 Arterial thrombosis Diseases 0.000 claims description 9
206010051055 Deep vein thrombosis Diseases 0.000 claims description 9
239000007943 implant Substances 0.000 claims description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
206010003658 Atrial Fibrillation Diseases 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 8
125000004438 haloalkoxy group Chemical group 0.000 claims description 8
230000002792 vascular Effects 0.000 claims description 8
206010002388 Angina unstable Diseases 0.000 claims description 7
208000007814 Unstable Angina Diseases 0.000 claims description 7
201000004332 intermediate coronary syndrome Diseases 0.000 claims description 7
206010008088 Cerebral artery embolism Diseases 0.000 claims description 6
206010008092 Cerebral artery thrombosis Diseases 0.000 claims description 6
206010014513 Embolism arterial Diseases 0.000 claims description 6
CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical group C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 6
206010063544 Renal embolism Diseases 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
230000002526 effect on cardiovascular system Effects 0.000 claims description 6
201000010849 intracranial embolism Diseases 0.000 claims description 6
239000000523 sample Substances 0.000 claims description 6
150000003536 tetrazoles Chemical class 0.000 claims description 6
201000005060 thrombophlebitis Diseases 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
206010037379 Pulmonary embolism and thrombosis Diseases 0.000 claims description 5
208000032109 Transient ischaemic attack Diseases 0.000 claims description 5
230000000747 cardiac effect Effects 0.000 claims description 5
230000034994 death Effects 0.000 claims description 5
208000027866 inflammatory disease Diseases 0.000 claims description 5
230000000302 ischemic effect Effects 0.000 claims description 5
201000010875 transient cerebral ischemia Diseases 0.000 claims description 5
208000030831 Peripheral arterial occlusive disease Diseases 0.000 claims description 4
238000001631 haemodialysis Methods 0.000 claims description 4
230000000322 hemodialysis Effects 0.000 claims description 4
230000000306 recurrent effect Effects 0.000 claims description 4
150000003852 triazoles Chemical group 0.000 claims description 4
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims description 2
230000002612 cardiopulmonary effect Effects 0.000 claims description 2
150000002473 indoazoles Chemical group 0.000 claims description 2
LBUJPTNKIBCYBY-UHFFFAOYSA-N tetrahydroquinoline Natural products C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 claims description 2
208000005764 Peripheral Arterial Disease Diseases 0.000 claims 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 45
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract description 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 abstract 1
125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 1
239000000543 intermediate Substances 0.000 description 187
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
238000006243 chemical reaction Methods 0.000 description 90
239000000243 solution Substances 0.000 description 90
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 84
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
239000000203 mixture Substances 0.000 description 74
235000019439 ethyl acetate Nutrition 0.000 description 61
239000007787 solid Substances 0.000 description 59
235000002639 sodium chloride Nutrition 0.000 description 56
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
239000003146 anticoagulant agent Substances 0.000 description 50
239000003795 chemical substances by application Substances 0.000 description 50
238000004128 high performance liquid chromatography Methods 0.000 description 50
238000005160 1H NMR spectroscopy Methods 0.000 description 48
239000012267 brine Substances 0.000 description 47
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 47
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 46
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
239000011541 reaction mixture Substances 0.000 description 41
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 41
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 36
239000002904 solvent Substances 0.000 description 35
239000002253 acid Substances 0.000 description 34
239000007832 Na2SO4 Substances 0.000 description 32
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
239000003814 drug Substances 0.000 description 32
229910052938 sodium sulfate Inorganic materials 0.000 description 32
235000011152 sodium sulphate Nutrition 0.000 description 32
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
210000001772 blood platelet Anatomy 0.000 description 28
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
235000019341 magnesium sulphate Nutrition 0.000 description 26
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 26
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
238000000746 purification Methods 0.000 description 23
108010074864 Factor XI Proteins 0.000 description 22
238000005481 NMR spectroscopy Methods 0.000 description 22
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IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
238000002360 preparation method Methods 0.000 description 20
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
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238000005345 coagulation Methods 0.000 description 18
238000012360 testing method Methods 0.000 description 18
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KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
238000004007 reversed phase HPLC Methods 0.000 description 16
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

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Heart & Thoracic Surgery (AREA)
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Diabetes (AREA)
Hematology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Other In-Based Heterocyclic Compounds (AREA)

ES12778912.1T 2011-10-14 2012-10-12 Compuestos de tetrahidroisoquinolina sustituidos como inhibidores del factor XIa Active ES2572908T3 (es)

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US201161547305P	2011-10-14	2011-10-14
US201161547305P		2011-10-14
PCT/US2012/059859 WO2013055984A1 (en)	2011-10-14	2012-10-12	Substituted tetrahydroisoquinoline compounds as factor xia inhibitors

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US (5)	US9108951B2 (de)
EP (2)	EP2766345B1 (de)
JP (1)	JP6033317B2 (de)
CN (1)	CN103987697B (de)
ES (2)	ES2572908T3 (de)
IN (1)	IN2014CN02806A (de)
WO (1)	WO2013055984A1 (de)

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2012
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- 2012-10-12 EP EP12778912.1A patent/EP2766345B1/de not_active Not-in-force
- 2012-10-12 ES ES12778912.1T patent/ES2572908T3/es active Active
- 2012-10-12 US US14/350,417 patent/US9108951B2/en active Active
- 2012-10-12 IN IN2806CHN2014 patent/IN2014CN02806A/en unknown
- 2012-10-12 JP JP2014535894A patent/JP6033317B2/ja not_active Expired - Fee Related
- 2012-10-12 EP EP14195397.6A patent/EP2899183B1/de not_active Not-in-force
- 2012-10-12 CN CN201280061670.3A patent/CN103987697B/zh not_active Expired - Fee Related
- 2012-10-12 ES ES14195397T patent/ES2699226T3/es active Active
2015
- 2015-07-15 US US14/799,681 patent/US9394276B2/en active Active
2016
- 2016-06-15 US US15/183,051 patent/US9725435B2/en active Active
2017
- 2017-07-07 US US15/643,891 patent/US10000466B2/en active Active
2018
- 2018-05-17 US US15/982,038 patent/US10906886B2/en active Active

Also Published As

Publication number	Publication date
US9108951B2 (en)	2015-08-18
CN103987697B (zh)	2017-04-26
US20140275061A1 (en)	2014-09-18
US20160289209A1 (en)	2016-10-06
US9394276B2 (en)	2016-07-19
US9725435B2 (en)	2017-08-08
US20150315200A1 (en)	2015-11-05
JP2014528479A (ja)	2014-10-27
EP2766345B1 (de)	2016-03-16
CN103987697A (zh)	2014-08-13
WO2013055984A1 (en)	2013-04-18
JP6033317B2 (ja)	2016-11-30
US10000466B2 (en)	2018-06-19
EP2899183A1 (de)	2015-07-29
US20180265494A1 (en)	2018-09-20
IN2014CN02806A (de)	2015-07-03
EP2766345A1 (de)	2014-08-20
US20170305880A1 (en)	2017-10-26
ES2699226T3 (es)	2019-02-08
EP2899183B1 (de)	2018-09-19
US10906886B2 (en)	2021-02-02

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